From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.

An overview of elastography - an emerging branch of medical imaging.

Elastography is emerging as an imaging modality that can distinguish normal versus diseased tissues via their biomechanical properties. This paper reviews current approaches to elastography in three areas—quasi-static, harmonic and transient—and describes inversion schemes for each elastographic imaging approach. Approaches include first-order approximation methods; direct and iterative inversion schemes for linear elastic; isotropic materials and advanced reconstruction methods for recovering parameters that characterize complex mechanical behavior. The paper's objective is to document efforts to develop elastography within the framework of solving an inverse problem, so that elastography may provide reliable estimates of shear modulus and other mechanical parameters. We discuss issues that must be addressed if model-based elastography is to become the prevailing approach to quasi-static, harmonic and transient elastography: (1) developing practical techniques to transform the ill-posed problem with a well-posed one; (2) devising better forward models to capture the complex mechanical behavior of soft tissues and (3) developing better test procedures to evaluate the performance of modulus elastograms.

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Model-based elastography: a survey of approaches to the inverse elasticity problem

The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and β-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of β-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by β-catenin nuclear translocation after 15 days. As a consequence, increased expression of β-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic β-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity.

Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure

Quasi-Static Ultrasound Elastography.

Elastography has emerged as a useful adjunct tool for ultrasound diagnosis. Elastograms are images of tissue stiffness and may be in color, grayscale, or a combination of the two. The first and most common application of elastography is for the diagnosis of breast lesions where studies have

Elastography: current status, future prospects, and making it work for you.

Recently, the feasibility of visualizing the characteristics of bonding at an inclusion-background boundary using axial-shear strain elastography was demonstrated. In this paper, we report a feasibility study on the utility of the axial-shear strain elastograms in the classification of in vivo breast tumor as being benign or malignant. The study was performed using data sets obtained from 15 benign and 15 malignant cases that were biopsy proven. A total of three independent observers were trained, and their services were utilized for the study. A total of 9 cases were used as training set and the remaining cases were used as testing set. The feature from the axial-shear strain elastogram, namely, the area of the axial-shear region, was extracted by the observers. The observers also outlined the tumor area on the corresponding sonogram, which was used to normalize the area of the axial-shear strain region. There are several observations that can be drawn from the results. First, the result indicates that the observers consistently (~82% of the cases) noticed the characteristic pattern of the axial-shear strain distribution data as predicted in the previous simulation studies, i.e. alternating regions of positive and negative axial-shear strain values around the tumor–background interface. Second, the analysis of the result suggests that in approximately 57% of the cases in which the observers did not visualize tumor in the sonogram, the elastograms helped them to locate the tumor. Finally, the analysis of the result suggests that for the discriminant feature value of 0.46, the number of unnecessary biopsies could be reduced by 56.3% without compromising on sensitivity and on negative predictive value (NPV). Based on the results in this study, feature values greater than 0.75 appear to be indicative of malignancy, while values less than 0.46 to be indicative of benignity. Feature values between 0.46 and 0.75 may result in an overlap between benign and malignant cases.

http://iopscience.iop.org/article/10.1088/0031-9155/53/17/022/pdf

Breast tumor classification using axial shear strain elastography: a feasibility study

Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

https://iopscience.iop.org/article/10.1088/0031-9155/52/21/013/pdf

The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo.

The purpose of this work was to investigate the potential of the normalized axial-shear strain area (NASSA) feature, derived from axial-shear strain elastograms (ASSE), for breast lesion classification of fibroadenoma and cancer. This study consisted of previously acquired in vivo digital radiofrequency data of breast lesions. A total of 33 biopsy-proven malignant tumors and 30 fibroadenoma cases were included in the study, which involved three observers blinded to the original BIRADS-ultrasound scores. The observers outlined the lesions on the sonograms. The ASSEs were segmented and color-overlaid on the sonograms, and the NASSA feature from the ASSE was computed semi-automatically. Receiver operating characteristic (ROC) curves were then generated and the area under the curve (AUC) was calculated for each observer performance. A logistic regression classifier was built to compare the improvement in the AUC when using BIRADS scores plus NASSA values as opposed to BIRADS scores alone. BIRADS score ROC had an AUC of 0.89 (95% CI = 0.81 to 0.97). In comparison, the average of the AUC for all the three observers using ASSE feature alone was 0.84. However, the AUC increased to 0.94 (average of 3 observers) when BIRADS score and ASSE feature were combined. The results demonstrate that the NASSA feature derived from ASSE has the potential to improve BIRADS breast lesion classification of fibroadenoma and malignant tumors.

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Louise M Mobbs

Papers

Breast tumor classification using axial shear strain elastography: a feasibility study

The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo.

Axial-shear strain elastography for breast lesion classification: further results from in vivo data

Optimizing precompression and compression levels to achieve maximum lesion contrast in breast elastography